Enterotoxigenic E. coli (ETEC) is the leading cause of diarrheal disease among children less than three years of age in developing countries and in travelers to these areas, with over 200 million cases annually, and 380,000 associated deaths. ETEC is transmitted by food or water contaminated with feces, and illness is characterized by profuse watery diarrhea lasting for several days to weeks. Prophylactic prevention of ETEC disease is currently unavailable, and antibiotic-resistant strains of ETEC have emerged. Triton Animal Products, Inc. is developing a therapeutic protein, mammary-associated serum amyloid A3 (MAA) that may offer prophylactic protection against ETEC infections. MAA is an orally-active, evolutionarily conserved protein present in colostrum - an early form of breast milk. MAA is an innate immune factor that stimulates intestinal epithelial cells to secrete mucin, which provides a natural protective barrier that inhibits adherence and colonization of enteropathogens, including E. coli. Triton's recombinant protein expression platform, a green alga, is edible, inexpensive, scalable, and safe, thus negating the need for expensive protein purification. Based on preliminary data, we estimate that algal-produced MAA can be made for approximately 4cent per dose. Our technology will enable the oral delivery of bioactive MAA to travelers, deployed service members, and at-risk children living in developing countries, to reduce the incidence of ETEC disease. Post-weaned pigs will be used as an animal model for human ETEC disease to determine effective MAA dosing and timing of administration for the prevention of infections. Furthermore, we will investigate a second- generation therapeutic - a genetic fusion between MAA and a natural antimicrobial peptide also present in colostrum - that has the potential to offer both prophylactic protection from infection and antimicrobial activities to prevent and treat disease.